9-127709552-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001012502.3(CFAP157):c.292A>C(p.Ile98Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CFAP157 NM_001012502.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.58

Genes affected

CFAP157 (HGNC:27843): (cilia and flagella associated protein 157) Predicted to enable microtubule binding activity. Predicted to be involved in sperm axoneme assembly. Located in cytosol; intracellular membrane-bounded organelle; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

PTRH1 (HGNC:27039): (peptidyl-tRNA hydrolase 1 homolog) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38316685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP157	NM_001012502.3	c.292A>C	p.Ile98Leu	missense_variant	2/9	ENST00000373295.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP157	ENST00000373295.7	c.292A>C	p.Ile98Leu	missense_variant	2/9	5	NM_001012502.3	P2
PTRH1	ENST00000335223.5	c.205+5883T>G		intron_variant		1
CFAP157	ENST00000614677.1	c.292A>C	p.Ile98Leu	missense_variant	2/9	2		A2
CFAP157	ENST00000496009.5	n.335A>C		non_coding_transcript_exon_variant	2/8	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 249498 Hom.: 0 AF XY: 0.0000222 AC XY: 3 AN XY: 135384

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461814 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727208

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2024

The c.292A>C (p.I98L) alteration is located in exon 2 (coding exon 2) of the CFAP157 gene. This alteration results from a A to C substitution at nucleotide position 292, causing the isoleucine (I) at amino acid position 98 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	18
Dann	Uncertain	0.98
DEOGEN2	Benign	0.069	T;.
Eigen	Benign	0.041
Eigen_PC	Benign	0.085
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.38	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.96	D
PROVEAN	Benign	-1.3	N;.
REVEL	Benign	0.13
Sift	Benign	0.13	T;.
Sift4G	Benign	0.49	T;T
Polyphen		0.67	P;.
Vest4		0.49
MutPred		0.27		Gain of disorder (P = 0.1107);Gain of disorder (P = 0.1107);
MVP		0.49
MPC		0.37
ClinPred		0.35	T
GERP RS		5.1
Varity_R		0.11
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs757606132; hg19: chr9-130471831;